The survival of preterm babies had increased over the past 2 decades especially for babies less than 28 weeks gestational age in developed countries [4] however the survival in developing countries at similar gestational age is still catching up. Recent studies have revealed that median survival of VLBW babies in India is as high as 88% [5].There is no comparative study of preterm survival between a level 3 centre in the U.K(country with advanced neonatal care) and comparable tertiary care centre in India. This study was intended to make such comparison. In our study the overall survival rate is 87.2% and 83% (p = 0.091) in U.K and Indian cohort respectively which perhaps is not the true reflection between two cohorts. When the survival according to gestational age was analysed there is a wide discrepancy in survival rate of babies ≤ 28 weeks. Survival at 23 weeks, 24 weeks, 25 weeks, 26 weeks and 27 weeks is 62% vs nil, 73.9% vs 33%, 78.9%vs 50%, 86.5% vs 45.2%, 91.3% vs 79.3% in U.K and Indian Cohort respectively. The survival of babies at the U.K study centre is comparable or slightly better for babies born at 25 to 30 weeks and significantly better for ≤ 24 weeks gestational age when compared to gestation specific survival statistics for England [17] (p < 0.001) (Table 4). Similarly when the Indian study centre was compared to a similar centre data [18] (due to paucity of overall national published data for gestation specific mortality) from India, the outcomes were better in the Indian study centre with statistical significance (p < 0.001) at 28, 29 & 30 weeks’ gestation. There is obvious significant difference in survival outcomes for babies less than 28 weeks of gestational age between the two study centres studied from India and the UK. Lower rate of antenatal steroid cover in Indian centre may be an important factor for increased mortality. In India resuscitation guidelines for babies less than 28 weeks is an ethical conundrum. There are no strict ethical guidelines, poor parental acceptability, financial constraints, lack of robust support post discharge from the state, leave against medical advice (LAMA) before discharge are known factors [19]. In summary many non-medical factors will influence the outcome in Indian scenario.
Table 4
Comparison of survival by gestational age at discharge in two study centres with respective country’s data
Gestational age
|
Survival % UK study centre
|
Survival %
England overallµ
|
p value
|
Survival %
Indian study centre
|
Survival
%
Indian data#
|
p value
|
22
|
100 $
|
17.9
|
0.368
|
-
|
-
|
-
|
23
|
62.8
|
35.9
|
< 0.001*
|
-
|
|
-
|
≤ 24
|
-
|
-
|
-
|
20.0
|
9.1
|
0.541
|
24
|
79.3
|
58.6
|
< 0.001*
|
33.0
|
-
|
-
|
25
|
78.9
|
74,0
|
0.252
|
50.0
|
33.2
|
0.361
|
26
|
86.5
|
83.4
|
0.431
|
45.2
|
33.2
|
0.358
|
27
|
91.3
|
88.4
|
0.367
|
79.3
|
69.2
|
0.351
|
28
|
94.1
|
92.4
|
|
82.5
|
62.3
|
0.017*
|
29
|
98.8
|
95.7
|
0.169
|
96.2
|
80.0
|
0.017*
|
30
|
95.8
|
97.5
|
0.293
|
95.4
|
80.0
|
0.009*
|
*p value significant (p < 0.05) |
# Single centre data from All India Institute of medical science18 |
$ n = 1, at 22 weeks of gestation at Study centre |
µ Gestation specific survival percentage – England (2008–2014)17 |
Babies managed in the UK centre were more immature compared to babies treated in Indian centre. A significantly higher number of babies were IUGR in the UK centre. The catchment area of Homerton hospital has a large ethnic minority population, significant deprivation and maternal co-morbidities such as diabetes and hypertension. Networking hospitals also transfer women with pregnancy induced hypertension and fetal growth restriction for specialist care to Homerton, which could explain higher number of IUGR babies in the UK centre. When the major preterm morbidities were analysed the rates of BPD was higher in the U.K cohort (30% vs 16%) due to increased survival of babies ≤26 weeks of gestation compared to Indian cohort. EPICure 2 study [4] showed nearly 60% of babies ≤26 weeks had BPD. Studies from India [20,21] reported an incidence of BPD of 28.7%, 10.7% & 11.2% in infants less than 28 weeks, 29-30 weeks and 31-32 weeks respectively The BPD rates from Indian centre in this study is lower than reported studies from India. Necrotising enterocolitis ≥stage 2 is 11.5% and 12.6% in U.K and Indian cohort, results are comparable to the previous studies [23].Number of babies with severe Retinopathy of Prematurity (ROP) and number of ROP needing treatment with laser or Avastin was significantly higher in Indian centre (12.9% vs 7.7%) despite higher gestational age of cohort than the UK centre possibly explained by difference in practices or higher risk factors. EPICure study [4] from the UK has shown an increased incidence of ROP needing treatment (Laser/Avastin) from 13% to 22%, however data from India for babies with ROP needing treatment (laser/Avastin) is between 16.6-20.7%[23,24]. Intraventricular haemorrhage grade 2 and above was 15.6% and 8.2% (p < 0.001) in U.K and India respectively which is slightly less than the previous studies [4,25].
Significantly higher number of babies from Indian centre (32.3% vs 10.7%) received treatment (medical and surgical) for Patent Ductus Arteriosus (PDA). EPICure 2 study [4] revealed about 51% of babies ≤26 weeks received treatment (medical/ surgical) during their stay in neonatal intensive care unit. The percentage of babies treated for PDA in Indian cohort is high due to low threshold for PDA closure. Both the centres used different criteria for PDA treatment decision. At Homerton hospital (UK centre), only ECHO confirmed symptomatic PDA in a ventilated baby received PDA treatment. In Indian centre, ECHO confirmed symptomatic PDA and needing oxygen >30% criteria was used. From various previous studies we know that PDA treatment rates depend on the individual centres, treating neonatologist and many other factors [26]
The proportion of mothers who received at least one complete course of antenatal steroids was 73.4% in the U.K cohort as compared to only 37.4% in Indian cohort. According to NNAP U.K 2016 data around 86% of eligible mothers received antenatal steroids [27] and in India there is wide variation in steroid uptake rate ranging from 48% to 74% [24,28] from previous studies . The low rate in Indian cohort perhaps presumed to be due to more high risk mother where there was not enough time to give antenatal steroid. There is clear evidence that antenatal steroid helps in reducing mortality and complications of prematurity in developed and developing world [29]. A significantly lower number of babies received surfactant during resuscitation at birth or any time during first 72 hours (86.9% versus 49.3%) in Indian centre; this may be because of babies in Indian cohort were of higher gestation and did not require surfactant, and arguably cost is also a factor. A study form India [30] reported around 43% of babies less than 32 weeks received surfactant. The risk factor of sepsis prior to delivery like preterm pre-labour rupture of membranes (pPROM) >24hours, foul smelling liquor, chorioamnionitis, maternal fever was found to be 11% in U.K cohort as compared to significant 43.6% (p<0.001) in Indian cohort. This corroborates with a significant postnatal blood culture proven sepsis (1.7% v 32.4%) in Indian cohort, it is known from previous studies the increased incidence of sepsis in Indian context [31].
In U.K due to regionalisation of neonatal care the proportion of babies delivered at specialist care centres improved from 18% to 49% and the survival of premature babies has improved from 88% to 93% [32]. On the contrary, in India there is no regionalisation of neonatal care. There are only few centres of excellence in public sector where majority of babies are born. The lack of robust transport facility or collaboration [33] between public and private sectors, inability to bear the high expenses of preterm babies, lack of universal insurance coverage compels the health care providers and parents to go for withdrawal of life supporting care or LAMA when faced with dilemma of treating babies less than 26weeks. The Government of India (GOI) through its National Health Mission (NHM) programme is providing many rural and urban districts now with special newborn care units (SNCUs) with provision for at least secondary level care along with providing trained manpower with the aim to reduce neonatal mortality rate (NMR) from the current 29 per 1000 live births to <10 per 1000 live births across the country by 2030 [34]. Since the start of NHM, 51% of pregnant women are receiving 4 or more antenatal visits and this has rose form 37% over past decade [35]. Improvement in coverage of antenatal check-up under NHM and uptake of antenatal steroids could perhaps leads to decrease in NMR as prematurity contributes to about 35% of neonatal mortality. Whether these strategies are enough or more robust strategies are needed like investing in advanced neonatal care (surfactant, CPAP, ventilators, parenteral nutrition) for extreme preterm babies is a question to reckon about.
Limitations
A large difference in sample size and significant difference in gestational age of babies managed between Indian and the UK centres. Details of antenatal care, day to day management of babies in NICU, details of early onset and late onset sepsis, death within 24 hours or labour ward deaths, and limitation of life supporting treatment (withdrawal, withholding or Do Not Resuscitate Order), leave against medical advice (LAMA), discharge weight and gestation were not studied. The other contributing factors such as family demographics, hospital settings including staff ratio to number of patients and level of staff training in neonatal medicine were not investigated.